PROJECT SUMMARY ? CENTRAL LABORATORY CORE The Central Laboratory Core (CLC) will be based in Seattle within the laboratory of Dr. Denise Galloway (co-chair of Trial 1) and include the robust services of our Shared Resources Facilities at the Fred Hutchinson Cancer Research Center (Fred Hutch). While Dr. Galloway is best known for her work on the role high-risk human papillomaviruses (HPV) play in anogenital cancers, her lab is broadly focused on the role that small DNA viruses play in cancer. To aid in epidemiologic studies, the Galloway lab has developed serologic assays to detect and characterize papillomavirus-specific antibodies. These latter assays will be conducted in the CLC for trials 1 and 3 (see below). The CLC will oversee and efficiently manage and coordinate acquisition and shipping of protocol- specified biological specimens (with relevant clinical data) to appropriate laboratories for testing and to the central tumor/specimen repository for storage of specimens for future correlative laboratory studies. Dr. Joseph (Jody) Carter will lead the Core, and manage the CLC in Seattle, and will be available to advise the LAC partner institutions, if required, on management of sample storage, testing, and shipping of protocol-specific specimens and storage of samples for current trial endpoints and for future studies. The Core will work with each trial team to develop standard-operating protocols (SOPs) for each protocol. Dr. Carter has over 25 years of experience as a laboratory leader and will help each of the trials develop consistent approaches to quality control for each of the laboratory assays. Laboratory and pathology oversite provided in the Laboratory Core will be effectively matrixed with effort provided by Fred Hutch personnel named within the trials. For example, the extensive work on HPV- specific memory B cell responses conducted by Dr. Galloway's lab is included in Trial 1 but shares personnel and objectives with the CLC. Placement of the CLC at the Fred Hutch will also allow access to Fred Hutch Shared Resources, for example, the Immunopathology Lab directed by Dr. Robert Pierce. Dr. Pierce is a Board-certified Anatomic Pathologist with a strong academic and industry background in immuno-oncology. His laboratory research is focused on mechanisms of tumor-induced immune tolerance by which tumors can escape anti-tumor immune responses, including natural and therapy-induced responses. He is expert in using multiparametric immunohistochemistry (IHC) panels to quantitatively analyze the phenotype and tissue distribution of immune cells within the tumor microenvironment, and in the development of biomarkers to predict responses to immuno-oncology treatments. Although the details of Trials 2 and 3 (delayed onset trials) will be finalized only after the grant is awarded, we anticipate the Dr. Pierce will participate in training and quality assurance for pathology for trials 2 and 3, and for the correlative studies proposed for trial 3.